Genetic testing improves the diagnoses of abnormalities in developing babies that are picked up during ultrasound scans, scientists report today (31 January) in The Lancet. Scientists from the Wellcome Sanger Institute, University of Cambridge, University of Birmingham, Great Ormond Street Hospital (GOSH) and their collaborators used genome sequencing to improve the diagnoses of abnormalities detected by ultrasound by around 10 per cent. Without genomic information, these abnormalities may not have been diagnosed until after pregnancy, if at all.

The findings suggest that if the results from genome sequencing can be delivered in the timeframe of a pregnancy, then the additional diagnosis can support the care, counselling and the family’s decision-making during pregnancy.

Approximately 3 per cent of pregnancies will have an abnormality in the structure of the developing baby, which is detected by a routine prenatal ultrasound scan. These can include problems with the baby’s heart, brain, skeleton or in some cases, multiple organs.

Having detected a problem with the baby’s development using prenatal ultrasound, parents will want to know the likely outcome for their child, however there can be many different possible causes of the abnormality.

In the largest study of its kind, researchers at the Wellcome Sanger Institute and their collaborators provided a genetic diagnosis for around 10 per cent of pregnancies with detected abnormalities. Without genetic testing, the genetic changes causing the developmental problem would not have been detected by standard diagnostic testing.

The research supports the mainstream use of more detailed genetic testing alongside other tests in order to provide better information to parents about how their child is likely to be affected.

“Genetic testing gets to the root cause of some of the problems seen in ultrasound scans and can give families much clearer answers about a baby’s condition. For example, a structural heart defect seen on an ultrasound scan could be caused by a disease that just affects the heart and may be relatively easily corrected, or it could be linked to something more complicated, such as neurological development, which could impact on the child’s schooling in the future.”

The research fell under the Prenatal Assessment of Genomes and Exomes (PAGE) study, which strives to gain a better understanding of genetic alterations, or variants, that cause developmental problems during pregnancy. The PAGE study aims to improve prenatal diagnostics, allow better genetics-derived prognoses and more informed parental counselling in the future.Scientists worked with a national network of fetal medicine and genetics clinics around the UK to recruit pregnant mothers with an ultrasound scan anomaly that had been detected, for participation in the study.

The team completed whole-exome sequencing* on 610 developing babies with detected abnormalities and 1206 biological parents. DNA samples from the pregnancies were taken during routine checks for other conditions, such as Down syndrome, through procedures such as amniocentesis and chorionic villous sampling.

Researchers identified new diagnoses of known genetic disorders for 52 of the 610 pregnancies, or 8.5 per cent. The team found that genetic diagnoses were considerably more common in fetuses with heart defects, skeletal abnormalities or multi-organ problems, which could lead to some ultrasound findings being prioritised for genetic testing.

“More genetic diagnoses were made for developing babies with problems surrounding the heart, skeleton or multiple organs, indicating that in the future genetic testing to make diagnoses may be tailored according to the type of problem.”

Professor Eamonn Maher, from the University of Cambridge

“The study shows that genome sequencing improves the diagnosis of genetic conditions in developing babies who have been found to have structural abnormalities during a routine ultrasound. Making these results available during pregnancy means we can offer better counselling to parents and enable access to appropriate care. The next step is to work on implementing this approach nationally so more families can benefit.”

Lyn Chitty, Professor of Genetics and Fetal Medicine at Great Ormond Street Hospital (GOSH) and the UCL Great Ormond Street Institute of Child Health (ICH)

“We hope that our research will aid NHS England’s ambition to roll out by next summer the use of invasive and then later non-invasive technology to perform exome sequencing in the generic or targeted screening of babies for congenital abnormalities during pregnancy.”

Professor Mark Kilby, of the University of Birmingham’s Institute of Metabolism and Systems Research and Clinical Lead in Fetal Medicine at Birmingham Women’s and Children’s NHS Foundation Trust

The results from this study were fed back to the families via their genetic counsellors to help them decide on treatment or management for the condition. Most of the diagnoses made were of conditions that have a low risk of recurrence in future pregnancies.

“When expectant parents are told from a scan that their baby is not developing as expected, it most often comes as a huge shock and they are anxious to know as much as possible about what is ahead. A genetic diagnosis can help provide them with important information about the outlook for their baby and whether they might face a similar situation in future pregnancies.”

Jane Fisher, Director of the Antenatal Results and Choices charity

Notes to Editors

*The genome is made up of genes that code for proteins (exons) and genes that do not code for proteins (introns). Together, all of the genes that code for proteins is known as the exome. Whole-exome sequencing is the process of reading the genetic code of the exome – all of the protein-coding genes, whereas whole-genome sequencing is the process of reading the genetic code of all genes in the genome.

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The University of Birmingham is ranked amongst the world’s top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, teachers and more than 5,000 international students from over 150 countries.

Birmingham Women’s and Children’s NHS Foundation Trust (BWC) brings together the very best in paediatric and women’s care in the region and is proud to have many UK and world-leading surgeons, doctors, nurses, midwives and other allied healthcare professionals on its team.

Birmingham Women’s Hospital is a centre of excellence, providing a range of specialist health care services to more than 50,000 women and their families every year from Birmingham, the West Midlands and beyond. As well as delivering over 8,200 babies a year, it offers a full range of gynaecological, maternity and neonatal care, as well as a comprehensive genetics service, which serves men and women. Its Fertility Centre is one of the best in the country, while the fetal medicine centre receives regional and national referrals. The hospital is also an international centre for education, research and development with a research budget of over £3 million per year and is proud to be home to a national miscarriage research centre – the first of its kind in the UK - in partnership with Tommy’s baby charity.

Birmingham Children’s Hospital is the UK’s leading specialist paediatric centre, caring for sick children and young people between 0 and 16 years of age. Based in the heart of Birmingham city centre, the hospital is a world leader in some of the most advanced treatments, complex surgical procedures and cutting edge research and development. The hospital is a nationally designated specialist centre for epilepsy surgery and also boasts a paediatric major trauma centre for the West Midlands, a national liver and small bowel transplant centre and a centre of excellence for complex heart conditions, the treatment of burns, cancer and liver and kidney disease.

Our Trust is also home to one of the largest Child and Adolescent Mental Health Services in the country, comprising of a dedicated inpatient Eating Disorder Unit and Acute Assessment Unit for regional referrals of children and young people with the most serious of problems (Tier 4) and the unique Forward Thinking Birmingham community mental health service for 0 to 25 year olds.

ARC is the only UK charity providing independent non-directive information and specialised support to women and couples through prenatal testing and its consequences. ARC also works closely and collaboratively with clinicians in the field and runs a well-established training programme for health care professionals. Find out more about ARC at www.arc-uk.org or follow us on Twitter: @ARCantenatal

The mission of the University of Cambridge is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. To date, 107 affiliates of the University have won the Nobel Prize.

Founded in 1209, the University comprises 31 autonomous Colleges, which admit undergraduates and provide small-group tuition, and 150 departments, faculties and institutions. Cambridge is a global university. Its 19,000 student body includes 3,700 international students from 120 countries. Cambridge researchers collaborate with colleagues worldwide, and the University has established larger-scale partnerships in Asia, Africa and America.

The University sits at the heart of the ‘Cambridge cluster’, which employs 60,000 people and has in excess of £12 billion in turnover generated annually by the 4,700 knowledge-intensive firms in and around the city. The city publishes 341 patents per 100,000 residents. www.cam.ac.uk

Founded in 1852, Great Ormond Street Hospital is one of the world’s leading children’s hospitals with the broadest range of dedicated, children’s healthcare specialists under one roof in the UK. With more than 252,000 outpatient and 43,000 inpatient visits every year, the hospital’s pioneering research and treatment gives hope to children from across the UK with the rarest, most complex and often life-threatening conditions. As an international centre of excellence in child healthcare, our patients and families are central to everything we do – from the moment they come through the door and for as long as they need us. www.gosh.nhs.uk/

The UCL Great Ormond Street Institute of Child Health (ICH) is part of the Faculty of Population Health Sciences within the School of Life and Medical Sciences at University College London. Together with its clinical partner Great Ormond Street Hospital for Children NHS Foundation Trust (GOSH), it forms the UK's only paediatric National Institute for Health Research Biomedical Research Centre and has the largest concentration of children's health research in Europe. For more information visit www.ucl.ac.uk/ich

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To celebrate its 25th year in 2018, the Institute sequenced 25 new genomes of species in the UK.

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